Is AFMID p.Asp247Asn (c.739G>A) pathogenic?

AFMID p.Asp247Asn (c.739G>A) is classified Uncertain significance in AFMID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely pathogenic (0.7347); Ultra-rare (popmax 0.0164%, mid).

How common is AFMID p.Asp247Asn (c.739G>A) in the general population?

AFMID p.Asp247Asn (c.739G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about AFMID p.Asp247Asn (c.739G>A)?

AlphaMissense predicts likely pathogenic (score 0.7347) — an in-silico prediction, not a clinical call.

AFMID p.Asp247Asn

c.739G>A · VCV3504691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7347 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7347	likely pathogenic · top 9% in AFMID
REVEL	0.442	indeterminate
SaProt	LLR -11.84	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.53 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00136% 22/1,611,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00891%	11,223
African / African-American	0.00534%	18,726
Finnishnot grpmax-eligible	0.00161%	62,014
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000932%	107,275

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.Asp247Asn
Coding: c.739G>A
MANE Select: NM_001010982
Type: single nucleotide variant
Location: chr17:78205697 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.39
Residue 247: an active site

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

Similar variants

AFMID p.Asp247Glu Uncertain significance ★ ⚠ same residue
AFMID p.Asp247Val Uncertain significance ★ ⚠ same residue
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.Cys237Gly Uncertain significance ★ ⚠ same type
AFMID p.Gln140Lys 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-asp247asn (accessed [today's date]).

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