Is FERMT3 p.Gln508Pro (c.1523A>C) pathogenic?

FERMT3 p.Gln508Pro (c.1523A>C) is classified Conflicting classifications of pathogenicity in FERMT3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-19). AlphaMissense: ambiguous (0.5625); Rare (popmax 0.436%, afr); Associated with Inborn genetic diseases.

What condition is associated with FERMT3 p.Gln508Pro (c.1523A>C)?

FERMT3 p.Gln508Pro (c.1523A>C) is associated with Inborn genetic diseases, leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Gln508Pro (c.1523A>C) in the general population?

FERMT3 p.Gln508Pro (c.1523A>C) is rare (popmax 0.436%, afr) (gnomAD).

What do computational predictors say about FERMT3 p.Gln508Pro (c.1523A>C)?

AlphaMissense predicts ambiguous (score 0.5625) — an in-silico prediction, not a clinical call.

FERMT3 p.Gln508Pro

c.1523A>C · rs138031026 · VCV719757

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5625 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.436%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5625	ambiguous
REVEL	0.49	indeterminate
SaProt	LLR -10.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.86, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q512P vs ClinVar Q508P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.436% African / African-American · 327/74,966 alleles

Filtering AF 0.397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.382%

Overall 0.0218% 351/1,611,396 alleles · rare exomes 155/1,459,226 · genomes 196/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.436%	229
Remaining individualsnot grpmax-eligible	0.0192%	5,203
Middle Eastern	0.0165%	6,062
Admixed American	0.00837%	11,953
South Asian	0.0011%	90,778
European (non-Finnish)	0.000424%	235,862

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: FERMT3
Protein: p.Gln508Pro
Coding: c.1523A>C
MANE Select: NM_031471
dbSNP: rs138031026
Type: single nucleotide variant
Location: chr11:64220647 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 512 UniProt numbering: the ferm domain; an α-helix

Full FERMT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: leukocyte adhesion deficiency 3

Similar variants

FERMT3 p.Arg573Ter Pathogenic/Likely pathogenic ★★ same condition
FERMT3 p.Ala109Thr Uncertain significance ★★ ⚠ same condition
FERMT3 p.Ala338Val Uncertain significance ★★ ⚠ same condition
FERMT3 p.Ala570Thr Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg103Gln Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg111His Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg129His Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg179Leu Uncertain significance ★★ ⚠ same condition

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/fermt3-p-gln508pro (accessed [today's date]).

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