Is CFHR4 p.Asn210Ser (c.629A>G) pathogenic?

CFHR4 p.Asn210Ser (c.629A>G) is classified Benign/Likely benign in CFHR4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.0964); Common (popmax 82.9%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CFHR4 p.Asn210Ser (c.629A>G)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

CFHR4 p.Asn210Ser

Q: How common is CFHR4 p.Asn210Ser (c.629A>G) in the general population?

CFHR4 p.Asn210Ser (c.629A>G) is common (popmax 82.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.629A>G · rs7417769 · VCV1252690

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 82.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.71	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 -0.2	GERP 0.54
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.86 · regional, not allelic
Overall
CADD	2.095	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 82.9% East Asian · 37,121/44,770 alleles

Filtering AF 82.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.9%

Overall 68.5% 1,100,757/1,607,610 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	82.9%	1
Amishnot grpmax-eligible	82.9%	1
Finnishnot grpmax-eligible	80.7%	1
Admixed American	75.5%	1
European (non-Finnish)	69.8%	1
Remaining individualsnot grpmax-eligible	67.4%	1
South Asian	66.6%	2
Ashkenazi Jewishnot grpmax-eligible	63.4%	2
Middle Eastern	58%	2
African / African-American	28.1%	4

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: CFHR4
Protein: p.Asn210Ser
Coding: c.629A>G
MANE Select: NM_001201550
dbSNP: rs7417769
Type: single nucleotide variant
Location: chr1:196907328 (GRCh38)
Gene constraint: LOEUF 1.204 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75
Residue 210: a UniProt-annotated variant site (in); the sushi 4 domain

Full CFHR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR4 p.Asn210Lys Likely benign ★ same residue
CFHR4 p.Ala159Val Uncertain significance ★★ ⚠ same type
CFHR4 p.Arg40His Uncertain significance ★★ ⚠ same type
CFHR4 p.Ile318Thr Uncertain significance ★★ ⚠ same type
CFHR4 p.Ser199Tyr Uncertain significance ★★ ⚠ same type
CFHR4 p.Ser507Leu Uncertain significance ★★ ⚠ same type
CFHR4 p.Trp68Ter Uncertain significance ★★ same type
CFHR4 p.Tyr238Ser 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/cfhr4-p-asn210ser (accessed [today's date]).

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