Is AFMID p.Val111Leu (c.331G>C) pathogenic?

AFMID p.Val111Leu (c.331G>C) is classified Uncertain significance in AFMID (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely pathogenic (0.5732); Absent from gnomAD v4.1.

How common is AFMID p.Val111Leu (c.331G>C) in the general population?

AFMID p.Val111Leu (c.331G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFMID p.Val111Leu (c.331G>C)?

AlphaMissense predicts likely pathogenic (score 0.5732) — an in-silico prediction, not a clinical call.

AFMID p.Val111Leu

c.331G>C · rs2510923800 · VCV2244092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5732 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5732	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 20 kb · p 0.53 · regional, not allelic
Overall
CADD	23.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFMID
Protein: p.Val111Leu
Coding: c.331G>C
MANE Select: NM_001010982
dbSNP: rs2510923800
Type: single nucleotide variant
Location: chr17:78204678 (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-val111leu (accessed [today's date]).

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