Is CEP97 p.Ala271Thr (c.811G>A) pathogenic?

CEP97 p.Ala271Thr (c.811G>A) is classified Likely benign in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-29). AlphaMissense: ambiguous (0.3849); Rare (popmax 0.211%, sas).

How common is CEP97 p.Ala271Thr (c.811G>A) in the general population?

CEP97 p.Ala271Thr (c.811G>A) is rare (popmax 0.211%, sas) (gnomAD).

What do computational predictors say about CEP97 p.Ala271Thr (c.811G>A)?

AlphaMissense predicts ambiguous (score 0.3849) — an in-silico prediction, not a clinical call.

CEP97 p.Ala271Thr

c.811G>A · rs567184992 · VCV2198693

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3849 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.211%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3849	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -9.31	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	28.1	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 0.211% South Asian · 192/91,060 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.177%

Overall 0.0155% 250/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.21%	83
South Asiangrpmax	0.211%	474
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0208%	4,808
European (non-Finnish)	0.00254%	39,331
Admixed American	0.00167%	59,998

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CEP97
Protein: p.Ala271Thr
Coding: c.811G>A
MANE Select: NM_024548
dbSNP: rs567184992
Type: single nucleotide variant
Location: chr3:101755512 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89

Full CEP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP97 p.Ala164Thr Uncertain significance ★★ ⚠ same type
CEP97 p.Ala624Gly Uncertain significance ★★ ⚠ same type
CEP97 p.Arg259Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg468Ile Uncertain significance ★★ ⚠ same type
CEP97 p.Arg570Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg585Cys Uncertain significance ★★ ⚠ same type
CEP97 p.Arg591Cys Uncertain significance ★★ ⚠ same type
CEP97 p.Arg615Cys 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/cep97-p-ala271thr (accessed [today's date]).

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