Is CCDC71 p.Asp437Val (c.1310A>T) pathogenic?

CCDC71 p.Asp437Val (c.1310A>T) is classified Uncertain significance in CCDC71 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: ambiguous (0.5392); Very rare (popmax 8.47e-05%, nfe).

How common is CCDC71 p.Asp437Val (c.1310A>T) in the general population?

CCDC71 p.Asp437Val (c.1310A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC71 p.Asp437Val (c.1310A>T)?

AlphaMissense predicts ambiguous (score 0.5392) — an in-silico prediction, not a clinical call.

CCDC71 p.Asp437Val

c.1310A>T · VCV4649637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5392 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5392	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -4.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,135 bp · p 0.091 · regional, not allelic
Overall
CADD	22.9	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 8.47e-05% European (non-Finnish) · 1/1,180,048 alleles

Overall 0.000137% 2/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)grpmax	8.47e-05%	1,180,048

Finnish 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: CCDC71
Protein: p.Asp437Val
Coding: c.1310A>T
MANE Select: NM_022903
Type: single nucleotide variant
Location: chr3:49162899 (GRCh38)
Gene constraint: LOEUF 1.135 · pLI 0.26 (gnomAD)
Structure: AlphaFold pLDDT 52.59

Full CCDC71 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC71 p.Ala106Pro Uncertain significance ★ ⚠ same type
CCDC71 p.Ala126Thr Uncertain significance ★ ⚠ same type
CCDC71 p.Ala128Val Uncertain significance ★ ⚠ same type
CCDC71 p.Ala132Ser Uncertain significance ★ ⚠ same type
CCDC71 p.Ala181Gly Uncertain significance ★ ⚠ same type
CCDC71 p.Ala246Pro Uncertain significance ★ ⚠ same type
CCDC71 p.Ala281Gly Uncertain significance ★ ⚠ same type
CCDC71 p.Ala283Asp 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/ccdc71-p-asp437val (accessed [today's date]).

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