Is CLEC14A p.Asp241Val (c.722A>T) pathogenic?

CLEC14A p.Asp241Val (c.722A>T) is classified Uncertain significance in CLEC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: likely benign (0.123); Very rare (popmax 0.00517%, nfe).

How common is CLEC14A p.Asp241Val (c.722A>T) in the general population?

CLEC14A p.Asp241Val (c.722A>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about CLEC14A p.Asp241Val (c.722A>T)?

AlphaMissense predicts likely benign (score 0.123) — an in-silico prediction, not a clinical call.

CLEC14A p.Asp241Val

c.722A>T · rs779870626 · VCV2616691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.123	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -10.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP -3.1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,469 bp · p 0.39 · regional, not allelic
Overall
CADD	7.028	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 0.00517% European (non-Finnish) · 61/1,180,014 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00397% 64/1,613,474 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,344
African / African-American	0.00267%	37,443
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: CLEC14A
Protein: p.Asp241Val
Coding: c.722A>T
MANE Select: NM_175060
dbSNP: rs779870626
Type: single nucleotide variant
Location: chr14:38255301 (GRCh38)
Gene constraint: LOEUF 1.883 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 69.00

Full CLEC14A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC14A p.Ser395= Benign ★★ same type
CLEC14A p.Ala140Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala155Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala186Val Uncertain significance ★ ⚠ same type
CLEC14A p.Ala228Gly Uncertain significance ★ ⚠ same type
CLEC14A p.Ala233Val Uncertain significance ★ ⚠ same type
CLEC14A p.Ala257Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala308Pro 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/clec14a-p-asp241val (accessed [today's date]).

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