Is AFMID p.Ser62Asn (c.185G>A) pathogenic?

AFMID p.Ser62Asn (c.185G>A) is classified Uncertain significance in AFMID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1104); Very rare (popmax 0.000124%).

How common is AFMID p.Ser62Asn (c.185G>A) in the general population?

AFMID p.Ser62Asn (c.185G>A) is very rare (popmax 0.000124%) (gnomAD).

What do computational predictors say about AFMID p.Ser62Asn (c.185G>A)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

AFMID p.Ser62Asn

c.185G>A · VCV3504744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -3
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.53 · regional, not allelic
Overall
CADD	1.212	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000124%

Overall 0.000124% 2/1,614,010 alleles · very rare

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: AFMID
Protein: p.Ser62Asn
Coding: c.185G>A
MANE Select: NM_001010982
Type: single nucleotide variant
Location: chr17:78202529 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.39

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

Similar variants

AFMID p.Ala41Asp Uncertain significance ★ ⚠ same type
AFMID p.Arg238His Uncertain significance ★ ⚠ same type
AFMID p.Arg35Gln Uncertain significance ★ ⚠ same type
AFMID p.Asn291Lys Uncertain significance ★ ⚠ same type
AFMID p.Asp247Asn Uncertain significance ★ ⚠ same type
AFMID p.Asp247Glu Uncertain significance ★ ⚠ same type
AFMID p.Asp247Val Uncertain significance ★ ⚠ same type
AFMID p.Cys237Gly Uncertain significance ★ ⚠ same type

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/afmid-p-ser62asn (accessed [today's date]).

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