Is ALLC p.Cys290Arg (c.868T>C) pathogenic?

ALLC p.Cys290Arg (c.868T>C) is classified Benign in ALLC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-09). AlphaMissense: likely pathogenic (0.9044); Low-frequency (popmax 4.17%, afr).

How common is ALLC p.Cys290Arg (c.868T>C) in the general population?

ALLC p.Cys290Arg (c.868T>C) is low-frequency (popmax 4.17%, afr) (gnomAD).

What do computational predictors say about ALLC p.Cys290Arg (c.868T>C)?

AlphaMissense predicts likely pathogenic (score 0.9044) — an in-silico prediction, not a clinical call.

ALLC p.Cys290Arg

c.868T>C · rs6730396 · VCV780813

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9044 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.17%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9044	likely pathogenic · top 2% in ALLC
REVEL	0.614	indeterminate
SaProt	LLR -17.34	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 3.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.82 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 4.17% African / African-American · 3,094/74,198 alleles

Filtering AF 4.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 4%

Overall 0.224% 3,571/1,597,114 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.17%	24
Admixed American	0.352%	284
Remaining individualsnot grpmax-eligible	0.3%	333
Middle Eastern	0.0829%	1,206
South Asian	0.0103%	9,753
European (non-Finnish)	0.00632%	15,834

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.Cys290Arg
Coding: c.868T>C
MANE Select: NM_018436
dbSNP: rs6730396
Type: single nucleotide variant
Location: chr2:3701529 (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.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
ALLC p.Arg360His 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-cys290arg (accessed [today's date]).

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