Is AFMID p.Val203Met (c.607G>A) pathogenic?

AFMID p.Val203Met (c.607G>A) is classified Likely benign in AFMID (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.108); Ultra-rare (popmax 0.02%, amr).

How common is AFMID p.Val203Met (c.607G>A) in the general population?

AFMID p.Val203Met (c.607G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about AFMID p.Val203Met (c.607G>A)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

AFMID p.Val203Met

c.607G>A · rs779472218 · VCV3093232

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -11.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.2	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.53 · regional, not allelic
Overall
CADD	0.022	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 0.02% Admixed American · 12/59,992 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00353% 57/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,999
South Asian	0.0121%	8,281
Remaining individualsnot grpmax-eligible	0.008%	12,497
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
East Asian	0.00223%	44,892
European (non-Finnish)	0.0022%	45,386

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.Val203Met
Coding: c.607G>A
MANE Select: NM_001010982
dbSNP: rs779472218
Type: single nucleotide variant
Location: chr17:78205481 (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-val203met (accessed [today's date]).

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