Is CLMN p.Glu771Ala (c.2312A>C) pathogenic?

CLMN p.Glu771Ala (c.2312A>C) is classified Likely benign in CLMN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-27). AlphaMissense: likely benign (0.1143); Rare (popmax 0.759%, mid).

How common is CLMN p.Glu771Ala (c.2312A>C) in the general population?

CLMN p.Glu771Ala (c.2312A>C) is rare (popmax 0.759%, mid) (gnomAD).

What do computational predictors say about CLMN p.Glu771Ala (c.2312A>C)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

CLMN p.Glu771Ala

c.2312A>C · rs147963787 · VCV717456

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.759%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -7.61	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 1.1	GERP -2.6, phastCons 0.015
Regional constraint	o/e 0.94	unconstrained · MANE · 128 kb · p 0.024 · regional, not allelic
Overall
CADD	16.85	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 0.759% Middle Eastern · 46/6,062 alleles

Filtering AF 0.585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.523%

Overall 0.0854% 1,378/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.759%	132
Admixed American	0.227%	441
South Asian	0.192%	520
Remaining individualsnot grpmax-eligible	0.109%	919
European (non-Finnish)	0.0789%	1,267
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
African / African-American	0.0173%	5,772

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: CLMN
Protein: p.Glu771Ala
Coding: c.2312A>C
MANE Select: NM_024734
dbSNP: rs147963787
Type: single nucleotide variant
Location: chr14:95203037 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.84
Residue 771: the 'disordered' region

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

Similar variants

CLMN c.2511+10C>T Benign ★★ same type
CLMN c.886-4G>T Likely benign ★★ same type
CLMN p.Asp592= Benign ★★ same type
CLMN p.Glu276Lys Likely benign ★★ same type
CLMN p.Glu357Lys Benign ★★ same type
CLMN p.His518= Benign ★★ same type
CLMN p.Ile900Phe Benign ★★ same type
CLMN p.Leu111= Benign ★★ 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/clmn-p-glu771ala (accessed [today's date]).

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