Is ANKRD30A p.Arg485Leu (c.1454G>T) pathogenic?

ANKRD30A p.Arg485Leu (c.1454G>T) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). AlphaMissense: likely benign (0.1643); Low-frequency (popmax 3.53%, mid).

How common is ANKRD30A p.Arg485Leu (c.1454G>T) in the general population?

ANKRD30A p.Arg485Leu (c.1454G>T) is low-frequency (popmax 3.53%, mid) (gnomAD).

What do computational predictors say about ANKRD30A p.Arg485Leu (c.1454G>T)?

AlphaMissense predicts likely benign (score 0.1643) — an in-silico prediction, not a clinical call.

ANKRD30A p.Arg485Leu

c.1454G>T · rs200164455 · VCV2333106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1643 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.53%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1643	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.2	GERP -1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 39 kb · p 0.0028 · regional, not allelic
Overall
CADD	7.087	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 3.53% Middle Eastern · 163/4,622 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.92%

Overall 0.545% 7,580/1,391,758 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.53%	28
Finnishnot grpmax-eligible	3.33%	30
Admixed American	2.13%	47
African / African-American	1.53%	65
South Asian	1.17%	85
Ashkenazi Jewishnot grpmax-eligible	0.427%	234
East Asian	0.417%	240
Remaining individualsnot grpmax-eligible	0.404%	248
European (non-Finnish)	0.279%	358
Amishnot grpmax-eligible	0.183%	546

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: ANKRD30A
Protein: p.Arg485Leu
Coding: c.1454G>T
MANE Select: NM_052997
dbSNP: rs200164455
Type: single nucleotide variant
Location: chr10:37145055 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.16 · 1 PDB

Full ANKRD30A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD30A p.Ala1006Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1119Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala120Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1226Glu Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala122Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1273Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1298Ser Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala146Thr 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/ankrd30a-p-arg485leu (accessed [today's date]).

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