Is ANKRD31 p.Ser171Phe (c.512C>T) pathogenic?

ANKRD31 p.Ser171Phe (c.512C>T) is classified Uncertain significance in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1798); Ultra-rare (popmax 0.0275%, afr).

How common is ANKRD31 p.Ser171Phe (c.512C>T) in the general population?

ANKRD31 p.Ser171Phe (c.512C>T) is ultra-rare (popmax 0.0275%, afr) (gnomAD).

What do computational predictors say about ANKRD31 p.Ser171Phe (c.512C>T)?

AlphaMissense predicts likely benign (score 0.1798) — an in-silico prediction, not a clinical call.

ANKRD31 p.Ser171Phe

c.512C>T · VCV4106254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1798	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 0.16
Regional constraint	o/e 0.92	unconstrained · MANE · 168 kb · p 0.00044 · regional, not allelic
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% African / African-American · 20/72,800 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.00183% 28/1,531,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0275%	3,640
Admixed American	0.012%	8,313
Remaining individualsnot grpmax-eligible	0.00334%	29,931

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: ANKRD31
Protein: p.Ser171Phe
Coding: c.512C>T
MANE Select: NM_001372053
Type: single nucleotide variant
Location: chr5:75196136 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.08

Full ANKRD31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD31 p.Arg1353Gln Benign ★★ same type
ANKRD31 p.Asn192Ile Benign ★★ same type
ANKRD31 c.1565-2A>G Pathogenic ★ same type
ANKRD31 p.Gln329Ter Pathogenic ★ same type
ANKRD31 p.Ala1011Asp Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1021Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1294Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1302Thr 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/ankrd31-p-ser171phe (accessed [today's date]).

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