Is ALLC p.Val305Met (c.913G>A) pathogenic?

ALLC p.Val305Met (c.913G>A) is classified Likely benign in ALLC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0597); Very rare (popmax 0.00448%, eas).

How common is ALLC p.Val305Met (c.913G>A) in the general population?

ALLC p.Val305Met (c.913G>A) is very rare (popmax 0.00448%, eas) (gnomAD).

What do computational predictors say about ALLC p.Val305Met (c.913G>A)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

ALLC p.Val305Met

c.913G>A · VCV4274088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.51, phastCons 0.72
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.82 · regional, not allelic
Overall
CADD	7.047	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 0.00448% East Asian · 2/44,686 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000872% 14/1,605,002 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,343
African / African-American	0.00402%	24,900
Admixed American	0.00169%	59,110
South Asian	0.00112%	89,076
European (non-Finnish)	0.000596%	167,913

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: ALLC
Protein: p.Val305Met
Coding: c.913G>A
MANE Select: NM_018436
Type: single nucleotide variant
Location: chr2:3701574 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.83

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

Similar variants

ALLC p.Arg265Gln Benign ★★ same type
ALLC p.Cys290Arg Benign ★★ same type
ALLC p.Ala125Ser Uncertain significance ★ ⚠ same type
ALLC p.Ala202Thr Uncertain significance ★ ⚠ same type
ALLC p.Ala95Glu Uncertain significance ★ same type
ALLC p.Arg242Gln Uncertain significance ★ ⚠ same type
ALLC p.Arg242Trp Uncertain significance ★ ⚠ same type
ALLC p.Arg274Pro 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/allc-p-val305met (accessed [today's date]).

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