Is MYO7B p.Asp1972Asn (c.5914G>A) pathogenic?

MYO7B p.Asp1972Asn (c.5914G>A) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-12). AlphaMissense: likely benign (0.0862); Low-frequency (popmax 2.01%, nfe); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Asp1972Asn (c.5914G>A)?

MYO7B p.Asp1972Asn (c.5914G>A) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Asp1972Asn (c.5914G>A) in the general population?

MYO7B p.Asp1972Asn (c.5914G>A) is low-frequency (popmax 2.01%, nfe) (gnomAD).

What do computational predictors say about MYO7B p.Asp1972Asn (c.5914G>A)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

MYO7B p.Asp1972Asn

c.5914G>A · rs61748909 · VCV3041266

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.01%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MYO7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.375	indeterminate
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 0.69, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D1946N vs ClinVar D1972N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.01% European (non-Finnish) · 23,448/1,168,254 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.98%

Overall 1.81% 28,766/1,589,330 alleles · low-frequency exomes 26,602/1,437,082 · genomes 2,164/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	5.06%	20
European (non-Finnish)grpmax	2.01%	50
Remaining individualsnot grpmax-eligible	1.69%	59
Ashkenazi Jewishnot grpmax-eligible	0.731%	137
Admixed American	0.634%	158
Amishnot grpmax-eligible	0.548%	182
South Asian	0.381%	262
Middle Eastern	0.348%	288
African / African-American	0.265%	377

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7B
Protein: p.Asp1972Asn
Coding: c.5914G>A
MANE Select: NM_001393586
dbSNP: rs61748909
Type: single nucleotide variant
Location: chr2:127635815 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1946 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign same condition
MYO7B c.6123+9T>C Benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7b-p-asp1972asn (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown