Is CES4A p.Ala236Val (c.707C>T) pathogenic?

CES4A p.Ala236Val (c.707C>T) is classified Uncertain significance in CES4A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.2322); Very rare (popmax 0.00822%, nfe).

How common is CES4A p.Ala236Val (c.707C>T) in the general population?

CES4A p.Ala236Val (c.707C>T) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about CES4A p.Ala236Val (c.707C>T)?

AlphaMissense predicts likely benign (score 0.2322) — an in-silico prediction, not a clinical call.

CES4A p.Ala236Val

c.707C>T · VCV3832206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2322 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2322	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -11.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.3, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 20 kb · p 0.11 · regional, not allelic
Overall
CADD	18.26	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 0.00822% European (non-Finnish) · 97/1,179,956 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00607% 98/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,164
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: CES4A
Protein: p.Ala236Val
Coding: c.707C>T
MANE Select: NM_001364782
Type: single nucleotide variant
Location: chr16:67003086 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.64

Full CES4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CES4A p.Ala127Thr Uncertain significance ★ ⚠ same type
CES4A p.Ala158Val Uncertain significance ★ ⚠ same type
CES4A p.Ala185Glu Uncertain significance ★ ⚠ same type
CES4A p.Ala222Glu Uncertain significance ★ ⚠ same type
CES4A p.Ala224Thr Uncertain significance ★ ⚠ same type
CES4A p.Ala250Val Uncertain significance ★ ⚠ same type
CES4A p.Ala271Thr Uncertain significance ★ ⚠ same type
CES4A p.Arg111His 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/ces4a-p-ala236val (accessed [today's date]).

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