Is ARMS2 p.Ala69Ser (c.205G>T) pathogenic?

ARMS2 p.Ala69Ser (c.205G>T) is classified Benign in ARMS2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2019-10-17). AlphaMissense: likely benign (0.0982); Common (popmax 38.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with age related macular degeneration 8.

What condition is associated with ARMS2 p.Ala69Ser (c.205G>T)?

ARMS2 p.Ala69Ser (c.205G>T) is associated with age related macular degeneration 8 (ClinVar).

What do computational predictors say about ARMS2 p.Ala69Ser (c.205G>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

ARMS2 p.Ala69Ser

Q: How common is ARMS2 p.Ala69Ser (c.205G>T) in the general population?

ARMS2 p.Ala69Ser (c.205G>T) is common (popmax 38.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.205G>T · rs10490924 · VCV979

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 38.8%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 8

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -4.82	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 0.9	GERP 1.3, phastCons 0.008
Regional constraint	o/e 0.78	unconstrained · MANE · 2,202 bp · p 0.011 · regional, not allelic
Overall
CADD	15.87	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 38.8% East Asian · 17,384/44,840 alleles

Filtering AF 38.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.1%

Overall 23.1% 372,235/1,613,268 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	38.8%	3
South Asian	32%	3
Amishnot grpmax-eligible	28.9%	3
Admixed American	25.9%	4
Remaining individualsnot grpmax-eligible	24.1%	4
Finnishnot grpmax-eligible	23.8%	4
African / African-American	23.1%	4
European (non-Finnish)	21.6%	5
Middle Eastern	20.7%	5
Ashkenazi Jewishnot grpmax-eligible	20.5%	5

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: ARMS2
Protein: p.Ala69Ser
Coding: c.205G>T
MANE Select: NM_001099667
dbSNP: rs10490924
Type: single nucleotide variant
Location: chr10:122454932 (GRCh38)
Gene constraint: LOEUF 1.815 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.14
Residue 69: a UniProt-annotated variant site (in)

Full ARMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

age related macular degeneration 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARMS2 c.298-13A>G Benign/Likely benign ★★ same condition
ARMS2 c.298-13A>T Benign/Likely benign ★★ same condition
ARMS2 c.*107T>G Likely benign ★★ same condition
ARMS2 c.*373T>G Benign/Likely benign ★★ same condition
ARMS2 c.*45T>G Likely benign ★★ same condition
ARMS2 p.Arg38Ter Benign ★★ same condition
ARMS2 c.*251T>C Uncertain significance ★ same condition
ARMS2 c.*313G>C Uncertain significance ★ same condition

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/arms2-p-ala69ser (accessed [today's date]).

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