Is ANKRD7 p.Ala99Ser (c.295G>T) pathogenic?

ANKRD7 p.Ala99Ser (c.295G>T) is classified Uncertain significance in ANKRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.296); Very rare (popmax 0.00134%, afr).

How common is ANKRD7 p.Ala99Ser (c.295G>T) in the general population?

ANKRD7 p.Ala99Ser (c.295G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ANKRD7 p.Ala99Ser (c.295G>T)?

AlphaMissense predicts likely benign (score 0.296) — an in-silico prediction, not a clinical call.

ANKRD7 p.Ala99Ser

c.295G>T · VCV4108788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.296	likely benign
REVEL	0.62	indeterminate
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.42	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.065 · regional, not allelic
Overall
CADD	27.3	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 0.00134% African / African-American · 1/74,494 alleles

Overall 0.000125% 2/1,605,684 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,138
African / African-Americangrpmax	0.00134%	74,494

Remaining individuals 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: ANKRD7
Protein: p.Ala99Ser
Coding: c.295G>T
MANE Select: NM_019644
Type: single nucleotide variant
Location: chr7:118234701 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.97

Full ANKRD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD7 p.Ala68Thr Uncertain significance ★ ⚠ same type
ANKRD7 p.Arg124Cys Uncertain significance ★ ⚠ same type
ANKRD7 p.Arg124His Uncertain significance ★ ⚠ same type
ANKRD7 p.Arg22Gln Uncertain significance ★ ⚠ same type
ANKRD7 p.Arg22Pro Uncertain significance ★ ⚠ same type
ANKRD7 p.Asn20Lys Uncertain significance ★ ⚠ same type
ANKRD7 p.Asp117Asn Uncertain significance ★ ⚠ same type
ANKRD7 p.Gln17Lys 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/ankrd7-p-ala99ser (accessed [today's date]).

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