Is CELA3A p.Arg77Ser (c.231G>C) pathogenic?

CELA3A p.Arg77Ser (c.231G>C) is classified Likely benign in CELA3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1601); Ultra-rare (popmax 0.0681%, sas).

How common is CELA3A p.Arg77Ser (c.231G>C) in the general population?

CELA3A p.Arg77Ser (c.231G>C) is ultra-rare (popmax 0.0681%, sas) (gnomAD).

What do computational predictors say about CELA3A p.Arg77Ser (c.231G>C)?

AlphaMissense predicts likely benign (score 0.1601) — an in-silico prediction, not a clinical call.

CELA3A p.Arg77Ser

c.231G>C · rs376151116 · VCV3141923

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1601	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.2
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.55 · regional, not allelic
Overall
CADD	1.025	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 0.0681% South Asian · 62/91,002 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.00409% 66/1,612,270 alleles · ultra-rare exomes 64/1,461,068 · genomes 2/151,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0681%	1,468
Remaining individualsnot grpmax-eligible	0.00641%	15,609

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: CELA3A
Protein: p.Arg77Ser
Coding: c.231G>C
MANE Select: NM_005747
dbSNP: rs376151116
Type: single nucleotide variant
Location: chr1:22005665 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.09
Residue 77: the peptidase s1 domain

Full CELA3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELA3A p.Ala125Thr Uncertain significance ★ ⚠ same type
CELA3A p.Ala147Gly Uncertain significance ★ ⚠ same type
CELA3A p.Ala147Thr Uncertain significance ★ ⚠ same type
CELA3A p.Ala64Thr Uncertain significance ★ ⚠ same type
CELA3A p.Ala64Val Uncertain significance ★ ⚠ same type
CELA3A p.Arg115His Uncertain significance ★ ⚠ same type
CELA3A p.Arg179Gln Uncertain significance ★ ⚠ same type
CELA3A p.Arg179Trp 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/cela3a-p-arg77ser (accessed [today's date]).

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