Is ALLC p.Gly209Arg (c.625G>C) pathogenic?

ALLC p.Gly209Arg (c.625G>C) is classified Uncertain significance in ALLC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely pathogenic (0.7171); Very rare (popmax 0.00167%, amr).

How common is ALLC p.Gly209Arg (c.625G>C) in the general population?

ALLC p.Gly209Arg (c.625G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ALLC p.Gly209Arg (c.625G>C)?

AlphaMissense predicts likely pathogenic (score 0.7171) — an in-silico prediction, not a clinical call.

ALLC p.Gly209Arg

c.625G>C · VCV4640036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7171	likely pathogenic · top 9% in ALLC
REVEL	0.605	indeterminate
SaProt	LLR -13.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.82 · regional, not allelic
Overall
CADD	28.8	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 0.00167% Admixed American · 1/59,904 alleles

Overall 0.000124% 2/1,613,406 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,904
European (non-Finnish)	8.48e-05%	1,179,774

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.Gly209Arg
Coding: c.625G>C
MANE Select: NM_018436
Type: single nucleotide variant
Location: chr2:3695830 (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-gly209arg (accessed [today's date]).

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