Is AFMID p.Arg151Gln (c.452G>A) pathogenic?

AFMID p.Arg151Gln (c.452G>A) is classified Likely benign in AFMID (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely benign (0.0695); Very rare (popmax 0.00445%, eas).

How common is AFMID p.Arg151Gln (c.452G>A) in the general population?

AFMID p.Arg151Gln (c.452G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about AFMID p.Arg151Gln (c.452G>A)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

AFMID p.Arg151Gln

c.452G>A · VCV3840601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -5.1	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.53 · regional, not allelic
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.0013% 21/1,614,026 alleles · very rare exomes 19/1,461,886 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,447
Finnishnot grpmax-eligible	0.00312%	32,017
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,984
African / African-American	0.00134%	74,902
European (non-Finnish)	0.0011%	90,772

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.Arg151Gln
Coding: c.452G>A
MANE Select: NM_001010982
Type: single nucleotide variant
Location: chr17:78204885 (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-arg151gln (accessed [today's date]).

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