Is CEMIP p.Val323Met (c.967G>A) pathogenic?

CEMIP p.Val323Met (c.967G>A) is classified Benign in CEMIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0995); Rare (popmax 0.736%, afr).

How common is CEMIP p.Val323Met (c.967G>A) in the general population?

CEMIP p.Val323Met (c.967G>A) is rare (popmax 0.736%, afr) (gnomAD).

What do computational predictors say about CEMIP p.Val323Met (c.967G>A)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

CEMIP p.Val323Met

c.967G>A · rs77954040 · VCV724641

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.736%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.74	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 6.2	GERP 0.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 20 kb · p 0.24 · regional, not allelic
Overall
CADD	24.7	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 0.736% African / African-American · 552/75,024 alleles

Filtering AF 0.685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.665%

Overall 0.0538% 868/1,614,014 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.736%	136
Middle Eastern	0.132%	758
South Asian	0.0582%	1,718
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Admixed American	0.0333%	3,000
European (non-Finnish)	0.0175%	5,728

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: CEMIP
Protein: p.Val323Met
Coding: c.967G>A
MANE Select: NM_001293298
dbSNP: rs77954040
Type: single nucleotide variant
Location: chr15:80889473 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69
Residue 323: the 'necessary for its endoplasmic reticulum (er) retention and interaction with hspa5' region

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

Similar variants

CEMIP p.Val323Gly Uncertain significance ★ ⚠ same residue
CEMIP p.Ala33Val Uncertain significance ★★ ⚠ same type
CEMIP p.Gly870Asp Uncertain significance ★★ ⚠ same type
CEMIP c.1086+82T>A Benign ★★ same type
CEMIP c.1087-239G>A Benign ★★ same type
CEMIP c.1412-76G>A Benign ★★ same type
CEMIP c.1587+57A>G Benign ★★ same type
CEMIP c.1587+79G>A 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/cemip-p-val323met (accessed [today's date]).

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